There are a number of hitherto known antibiotics which are produced by microbials. However, only limited types of the known antibiotics have been used clinically in practice. In the fields of antimicrobial chemotherapy, β-lactam antibiotics such as penicillins and cephalosporins; aminoglycoside antibiotics such as kanamycins; and macrolide antibiotics such as erythromycin have been employed.
While, in the chemotherapy of bacterial infections, the emergence and the increase of antibiotic-resistant bacteria has involved a serious human health problem. Especially, bacterial infection of compromised hosts such as senior citizens and people who have chronic diseases is critical, and thus nosocomial bacterial infections of the inpatients can always invoke a social problem. In the chemotherapy of bacterial infections, the conventional antibiotic drugs do not show an appropriately high antibacterial activity against resistant Gram-positive bacteria such as methicillin-resistant strain of Staphylococcus aureus (hereinafter abbreviated as MRSA), vancomycin-resistant Enterococci (hereinafter abbreviated as VRE), penicillin-resistant strain of Streptococcus pneumoniae (hereinafter abbreviated as PRSP) and β-lactamase negative and ampicillin-resistant Haemophilus influenzae (hereinafter abbreviated as BLNAR). Therefore, these antibiotic-resistant bacteria can rise a management problem for the hospitals, that there are emerged nosocomial bacterial infections of patients. For the chemotherapeutic treatment of infection by MRSA, there have been employed arbekacin which is a kanamycin derivative, and vancomycin, but there is remaining a problem that new and more effective antibiotics continue to have been desired to be discovered and provided.
As will be clear from the foregoing situations, there is a keen need for discovery or innovation of new antibiotic therapeutic agent that has new and quite unique chemical structure, an enhanced efficacy, a high specificity and reduced side-effects.
An object of this invention is therefore to provide novel antibiotics which have excellent antibacterial activities and are capable of meeting the requisites as above-mentioned.
On the other hand, it is hitherto known that some microbials can produce 16-membered macrolactone compounds which have a conjugated diene structure along with the hemiacetal moiety and which are called macrobiolides. The known macrobiolides include elaiophylin (see Arcamone, F. M.; Bertazzoli, C.; Ghione, M.; Scotti, T. G; “Microbiol.”, Vol. 7, p. 207 (1959) and European patent application publications No. 6297,523A3 and No. 0315,003A3); azalomycin B (see Arai, M; “Antibiot” Ser. A, pp. 13, pp. 46, pp. 51 (1960); and Antibiotic 225 E (see Khlebarova, E. I.; Georgieva-Borisova, I. K.; Sheikova, G. N.; Blinov, N. O; “Farmatsiya (Sofia)” Vol. 22, p. 3 (1972). On the other hand, a known 16-membered macrolactone includes salbomycin (see German Patent application DE 3248280-A, published in 1972), though the structure of salbomycin is identical to that of elaiophylin.